NCCN Recommends Shorter Duration Chemotherapy for Stage III Colon Cancer in Order to Reduce Neurotoxicity

CancerConnect News: The National Comprehensive Cancer Network’s (NCCN’s) colon cancer guidelines have been changed to indicate that patients with low-risk stage III colon cancers can be treated with a shorter schedule of adjuvant chemotherapy. The changes were outlined at the recent National Comprehensive Cancer Network (NCCN) 23rd Annual Conference in March.

The change is based on results from the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) clinical study that evaluated 12,834 patients in 12 countries.1,2

IDEA compared 3 months of treatment with the standard of 6 months of oxaliplatin-based chemotherapy regimens. Treatment was with one of two oxaliplatin chemotherapy containing regimens which are currently the standard of care. In both treatments, oxaliplatin is associated with cumulative dose-dependent neurotoxicity

  • FOLFOX (leucovorin, fluorouracil, oxaliplatin)
  • CAPEOX (capecitabine/oxaliplatin; also known as XELOX).

Investigators randomly assigned 12,834 patients with stage III colon cancer to receive either 3 or 6 months of a chemotherapy regimen based on clinician/patient choice (this was not a comparison of the two regimens).

On average the difference in survival without cancer progression at 3 years from treatment was only lower by 0.9% for individuals treated with the 3-month chemotherapy regimen compared to those receiving 6 months of treatment.

There was a dramatic reduction in neurotoxicity with 3 months of treatment (reported by 17% patients on FOLFOX and 15% on CAPEOX, 15%) compared with 6 months (48% and 45%, respectively).

The NCCN guidelines now incorporate the 3-month regimen of adjuvant chemotherapy and their guidelines reflect the fact that different risk groups performed differently with the different regimens in the trial. Specifically, the NCCN’s stage III colon cancer treatment recommendations are differentiated on the basis of risk status:

  • Low-risk stage III is defined as pathologic stages T1-3N1. For these patients, the preferred treatments are CAPEOX for 3 months or FOLFOX for 3 to 6 months.
  • High-risk stage III disease is defined as pathologic stages T4N1-2 and AnyTN2. For these patients, the preferred treatments are CAPEOX for 3 to 6 months or FOLFOX for 6 months.

Patients with colon cancer that has spread to the lymph nodes (stage 3) usually get six months of chemotherapy after surgery. But researchers found that shortening treatment to three months did not affect the chance of cancer returning for many patients.

References:

  1. Grothey, A. et al. (2018) Duration of Adjuvant Chemotherapy for Stage III Colon Cancer. The New England Journal of Medicine. (link is external)
  2. Iveson, T. et al. (2018) 3 versus 6 months of adjuvant oxaliplatin-fluoropyrimidine combination therapy for colorectal cancer (SCOT): an international, randomised, phase 3, non-inferiority trial. Lancet Oncology.  (link is external)

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